Salivary Nitrate Maintains Mucosal Homeostasis via the Sialin–Neuropeptide Axis.

The article focuses on the role of salivary nitrate in promoting oral mucosal regeneration through a sialin-dependent sensory neuropeptide signaling axis. Using murine palatal wound models, the study demonstrates that depletion of salivary nitrate impairs wound healing by reducing epithelial proliferation, disrupting collagen organization, and suppressing growth factors such as vascular endothelial growth factor (VEGF) and transforming growth factor–β (TGF-β), effects reversible by nitrate supplementation. Mechanistically, nitrate enhances reinnervation of myelinated sensory nerves and stimulates secretion of neuropeptides including calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) via the nitrate transporter sialin (encoded by SLC17A5). Sensory neuron–specific deletion of sialin abolishes these regenerative effects, establishing sialin as essential for nitrate-mediated neural and epithelial repair. These findings identify a novel nitrate–sialin–neuropeptide pathway critical for oral mucosal homeostasis and suggest potential therapeutic targets for enhancing tissue repair.